Streptococcus suis, an important zoonotic pathogen capable of transmission from pigs to humans, represents a critical threat to both public health and the global pork industry. The increasing prevalence of multidrug-resistant S. suis strains, coupled with their ability to form biofilms, has necessitated the development of alternative antimicrobial strategies. In this study, we characterized the therapeutic potential of Ply113, an endolysin derived from an Enterococcus faecium phage, against S. suis. Ply113 has shown potent bactericidal activity against S. suis in vitro, with rapid time-kill characteristics and broad-spectrum efficiency against clinically prevalent serotypes (2, 3, 4, 7, and 9). Transmission electron microscopy analysis revealed that Ply113 induced distinct morphological alterations in S. suis, including cell wall disintegration and cytoplasmic leakage. This endolysin exhibited anti-biofilm functionality, eradicating biofilms formed by clinical strain of S. suis in a concentration-dependent manner. In murine models of bacteremia, a single administration of Ply113 provided complete protection against lethal S. suis infection, significantly decreasing the bacterial burden in the liver and spleen and attenuating organ injury. Additionally, Ply113 has been shown to be safe for mice, with no adverse effects. Taken together, our findings indicate that Ply113 is a promising alternative antimicrobial agent for combating biofilm-related infections caused by S. suis.

Keywords: Streptococcus suis; anti-biofilm activity; antibacterial activity; endolysin; phage.